Isotopes of rhenium have recently become of interest to the nuclear medicine community for use in diagnostic and therapeutic applications. Two isotopes of rhenium, .sup.186 Re and .sup.188 Re, are of particular significance due to their suitability for therapeutic and diagnostic applications. Both .sup.186 Re and .sup.188 Re are .beta.-emitting radionuclides (beta energies of 1.07 and 2.12 Mev, respectively) with relatively short half lives (90 hours for .sup.186 Re and 16.98 hours for .sup.188 Re). In addition, both exhibit gamma emissions (9.2%, 137 kev and 15%, 155 kev, respectively) suitable for gamma counter imaging of biodistribution in vivo.
.sup.186 Re is conventionally produced from .sup.185 Re (37% natural abundance) by neutron capture in a nuclear reactor. The nuclear properties of this isotopic system are as follows: ##STR1## In the production of .sup.186 Re, rhenium-185 metal is typically irradiated at a high flux rate, such as at 10.sup.14 -10.sup.15 neutrons/cm.sup.2 /s, for periods of 24 hours or more. After irradiation, the resulting .sup.186 Re isotope must be solubilized for clinical applications, such as for conjugation to tumor-specific antibodies, typically by treatment with a strong oxidizing agent, e.g., hydrogen peroxide or concentrated nitric acid, to obtain a soluble perrhenate solution. The perrhenate solution, containing .sup.186 Re, must then be neutralized and purified to remove contaminants prior to antibody conjugation and/or other clinical applications.
.sup.188 Re is conventionally derived from either natural rhenium-187 (63% natural abundance) in carrier-added form by neutron bombardment in a nuclear reactor or, preferably, in high specific activity, carrier-free form from a generator made of a target tungsten material, enriched in .sup.186 W, by double neutron capture in a high-flux reactor to produce .sup.188 W and its decay product .sup.188 Re. The nuclear properties of this isotopic system are as follows: ##STR2## Since .sup.188 Re produced from neutron capture by irradiation of .sup.187 Re is accompanied by unconverted .sup.187 Re and other impurities (i.e., is obtained in carrier added form) and since the short half-life of .sup.188 Re limits the efficiency of .sup.188 Re accumulation during relatively longer-term irradiation and subsequent handling procedures, the production of .sup.188 Re by nuclear decomposition in no carrier added form in a tungstate/rhenium generator system is highly preferred.
Previous tungsten/rhenium generators for the production of .sup.188 Re have consisted of small, alumina columns with relatively small amounts of tungsten targets adsorbed on the columns and, thus, low rhenium yields in the microcurie (.mu.Ci) range. To increase the amount of rhenium obtainable from such columns (i.e., in the millicurie range, mCi), larger column masses are necessary in order to contain larger amounts of target tungsten. These larger columns, in turn, require increased eluting volumes. In addition, prior .sup.188 W/.sup.188 Re generators using alumina columns have provided poor yields of .sup.188 Re and unacceptable levels of release, or "breakthrough", of .sup.188 Re from the column due primarily to the necessity of adsorbing large (0.5-2.0 grams) amounts of target tungsten (primarily as .sup.186 W) onto the alumina column.
U.S. Pat. No. 4,859,931 of Ehrhardt discloses an improved .sup.188 Re generator in which an insoluble zirconyl tungstate matrix containing .sup.188 W decays over time producing .sup.188 Re in the form of perrhenate (.sup.188 ReO.sub.4.sup.-), which is readily elutable from the matrix. The zirconyl tungstate matrix as disclosed in the Ehrhardt patent is produced by dissolving irradiated tungsten trioxide in a heated basic solution, adding the basic tungsten trioxide solution to an acidic zirconium-containing solution to obtain an acidic zirconyl tungstate slurry containing .sup.188 W, drying the slurry to form a permeable matrix, and then packing the matrix in an elutable column. The Ehrhardt generator has been found to be a highly effective generator of .sup.188 Re.
Although the direct irradiation of .sup.185 Re has proven effective for the production of .sup.186 Re, and both the direct irradiation of .sup.187 Re and the zirconyl tungstate generator system have proven to be effective for the production of .sup.188 Re, these systems have inherent drawbacks which limit their large-scale use and acceptability. In the case of direct irradiation of .sup.185 Re or .sup.187 Re, the irradiated .sup.186 Re or .sup.188 Re in the form of rhenium metal or rhenium trioxide must be solubilized, typically by oxidation with concentrated nitric acid, to form soluble perrhenate (ReO.sub.4.sup.-). The perrhenate solution must then be neutralized, such as with aqueous ammonia. This procedure not only is time consuming and requires extensive handling and processing of irradiated materials, but also results in unwanted by-products which must be separated from the perrhenate. Prior tungsten/rhenium generator systems for the production of .sup.188 Re also require significant handling and processing of irradiated materials, including dissolution, precipitation, filtration, drying, gel fragmentation and column packing steps, all occurring after irradiation of the tungsten metal or tungsten trioxide starting materials. These processing steps with irradiated materials necessitate the use of cumbersome shielded processing equipment, result in relatively high manufacturing costs and pose significant potential safety risks.
U.S. Pat. No. 4,778,672 of Deutsch et al. discloses a procedure for the purification of irradiated perrhenate and tungstate solutions, primarily to eliminate contaminants introduced through harsh conditions required for target dissolution. In the Deutsch et al. procedure, irradiated rhenium metal is dissolved by the addition of concentrated nitric acid and the resulting solution is neutralized with ammonia. The neutralized solution, containing solubilized perrhenate, is then treated with a soluble lipophilic counter ion, such as a solution of tetrabutyl ammonium bromide, and passed through a preferential sorption column, which has been pretreated with the counter ion, to separate the perrhenate from the solution. The retained perrhenate, which has been separated from unwanted byproducts formed in the rhenium dissolution process, is then eluted from the column. The foregoing procedure may also be employed in the purification of pertechnetate eluant obtained from a molybdenum-99/technetium-99 m generator column or perrhenate eluant from a tungsten-188/rhenium-188 generator column. The process of the Deutsch patent has been found to be effective for the removal of impurities from pertechnetate and perrhenate solutions. This process, however, is time consuming and further aggravates the costs and other problems associated with processing of irradiated materials. These problems remain particularly acute in connection with the production of .sup.186 Re which, due to its relatively short half-life and production by direct irradiation, must frequently be processed into suitable form on-site in a clinical or hospital setting.
In order to avoid some processing steps with irradiated materials in connection with the generator production of .sup.99m Tc in a related molybdenum/technetium generator system, Narasimhan et al., "A New Method for .sup.99m Tc Generator Preparation," J. Radioanal. Nucl. Chem., Letters, Vol. 85, No. 6, pp. 345-356, discloses an improved method of preparing a zirconium molybdate .sup.99m Tc generator in which the precipitation, filtration, drying and fragmentation of radioactive materials required in the preparation of a zirconium molybdate .sup.99m Tc generator are avoided by directly irradiating zirconium molybdate instead of molybdenum trioxide as in prior zirconium molybdate generator systems. However, the direct irradiation of zirconium molybdate as reported by Narasimhan et al. resulted in the production of radioactive contaminants unacceptable for clinical therapeutic or diagnostic applications, including .sup.97 Zr, .sup.95 Zr, .sup.175 Hf, .sup.181 Hf, and .sup.24 Na.
Thus, a strong need exists for improved irradiation targets for the production of .sup.186 Re and .sup.188 Re which will simplify the dissolution of these radionuclides or their precursors and reduce the handling procedures, costs and safety hazards associated with their production in a form suitable for medical diagnostic or therapeutic use.